CHICAGO (Reuters) - Doctors should prescribe the lowest
doses of Celebrex possible in patients at high risk of heart
problems, researchers who did a combined analysis of six
studies of the Pfizer Inc pain drug said on Monday.

The analysis suggests the potentially harmful effect of
Celebrex dosage is most pronounced in higher-risk patients,
researchers said at the American College of Cardiology
scientific meeting.

"Patients at low cardiovascular risk should take some level
of comfort," said Dr. Scott Solomon, lead researcher of the
National Cancer Institute-sponsored analysis. "That wasn't so
clear previously."

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Doctors should exercise caution in prescribing the drug,
generally known as celecoxib, in high-risk patients, said
Solomon, whose analysis was also published online in the
journal Circulation.

Celebrex belongs to a class of pain drugs known as cox-2
inhibitors and is the only such drug still on the market in the
United States. Merck and Co Inc withdrew its widely used cox-2
drug, Vioxx, from the market in 2004 after a study showed it
doubled the risk of heart attack and stroke in long- term
users.

Another cox-2 inhibitor from Pfizer called Bextra was also
pulled from the U.S. market due to safety concerns.

While the analysis sheds light on how the drug should be
used, Solomon said he could not judge whether the data lift the
cloud over this class of drugs.

The six trials involving a total of 7,950 patients all
studied Celebrex against a placebo for uses other than
arthritis. Patients received either 400 milligrams once a day,
200 mg twice a day, or 400 mg twice a day.

The primary goal of the pooled analysis was an assessment
of the combined risk of cardiovascular death, heart attack,
stroke, heart failure or events involving blood clots.

Researchers found the heart risk was lowest at the 400 mg
daily dose. They found nearly a two-fold risk of adverse heart
events with the 200 mg twice daily dose and that jumped to
about a three-fold risk at the 400 mg twice daily dose.

"Even 400 mg once a day showed elevated risk" in the
high-risk population, Solomon said, adding he could not
extrapolate whether doses lower than 400 mg cut risk further.

The increased risk was not affected by aspirin use,
researchers said.

"Most of the data used in this pooled analysis have
previously been published and are consistent with what we
already know about the cardiovascular risks of Celebrex and
other prescription arthritis pain relievers," said Gail
Cawkwell, Pfizer's executive medical director.

"The analysis doesn't provide any new conclusions on the
FDA-approved doses of Celebrex, including the most commonly
prescribed dose of 200 mg daily," she said.

Dr. Steven Nissen of the Cleveland Clinic, who has a study
on lower doses underway, added: "There aren't long-term
randomized placebo-controlled trials for that dose, The only
way we're ever going to answer these questions is with good
randomized prospective data," he said. "We'll tell it like it
is when the data is in."

(Writing and additional reporting by Bill Berkrot in New
York, and Julie Steenhuysen in Chicago, editing by Dave
Zimmerman/Andre Grenon)